Wang XJ et al. (2011) Bioorg Med Chem Lett "A novel macrocyclic lactone with insecticidal bioactivity from Streptomyces microflavus neau3."

Xiang WS, Wang JD, Wang XJ, Yan YJ, Zhang H, Gong DL, Liu CX, Zhang J

[Bioorg Med Chem Lett, 2011]

A novel macrocyclic lactone (1) was isolated from the fermentation broth of Streptomycesmicroflavus neau3, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed high acaricidal activity against adult mites (IC(50)=11.1 g mL(-1)), and nematocidal activity against Caenorhabditis elegans (IC(50)=17.4 g mL(-1)), especially the acaricidal activity against mite eggs with an IC(50) of 37.1 g mL(-1), which was relative higher than that of the commercial acaricide and nematocide milbemycins A(3)/A(4).

Wang XJ et al. (2010) J Agric Food Chem "Isolation and identification of novel macrocyclic lactones from Streptomyces avermitilis NEAU1069 with acaricidal and nematocidal activity."

Wang XJ, Wang JJ, Wang JD, Jiang L, Wang M, Xiang WS

[J Agric Food Chem, 2010]

Bioactivity-guided fractionation of Streptomyces avermitilis NEAU1069 fermentation broth was used to isolate and determine the chemical identity of bioactive constituents with acaricidal and nemotocidal activity. The structures of novel compounds 1 and 2 were determined on the basis of spectroscopic analysis, including 1D and 2D NMR as well as HRESI-MS, ESI-MS of spectrometry analysis, UV and IR spectroscopic analyses, and comparison with data from the literature. The acaricidal activities of the isolated compounds against adult mites and mite eggs were evaluated by mortality and unhatched eggs. The nematocidal activity of the isolated compounds against Caenorhabditis elegans was calculated according to the immobilized rates against the total number of tested nematodes. The results indicated that compounds 1 and 2 exhibited potent acaricidal activity against adult mites, with a mortality of >90% at a concentration of 30 microg/mL. However, compounds 1 and 2 showed only weak acaricidal activity against mite eggs, with unhatched mite egg rates of <60% at a concentration of 100 microg/mL. Compound 2, a hydroxylated derivative at C-23 of 1, possessed a high nematocidal activity against C. elegans, with an immobility of >90% at a concentration of 10 microg/mL. These results demonstrate that compounds 1 and 2, especially compound 2, have potential as pesticides with acaricidal and nematocidal activity.

Infarinato N (2019) J Cell Biol "Xiaochen Wang: Building up our understanding of breaking down."

Infarinato N

[J Cell Biol, 2019]

Wang studies lysosomal degradation pathways using <i>C. elegans</i> as a model system.

Wang JT et al. (2014) Curr Biol "P granules."

Seydoux G, Wang JT

[Curr Biol, 2014]

Wang and Seydoux discuss the functional importance of P granules - the germline-specific RNA granules of C. elegans.

Munro E (2017) Dev Cell "Protein Clustering Shapes Polarity Protein Gradients."

Munro E

[Dev Cell, 2017]

In this issue of Developmental Cell, Dickinson etal. (2017) and Rodriguez etal. (2017), along with Wang etal. (2017) in Nature Cell Biology, show how PAR protein oligomerization can dynamically couple protein diffusion and transport by cortical flow to control kinase activity gradients and polarity in the C.elegans zygote.

Rashid S et al. (2017) Dev Cell "Packing on the Pounds in Response to Bacterial Growth Conditions."

Rashid S, MacNeil LT

[Dev Cell, 2017]

Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C.elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.

Xiang WS et al. (2010) J Antibiot (Tokyo) "New nemadectin congener from Streptomyces microflavus neau3: fermentation, isolation, structure elucidation and biological activities."

Xiang WS, Wang JD, Wang M, Wang XJ

[J Antibiot (Tokyo), 2010]

Bioactivity-guided fractionation of Streptomyces microflavus neau3 fermentation broth was used to determine the chemical identity of bioactive constituents. The structure of the new compound 1 was determined on the basis of spectroscopic analysis, including 1D and 2D NMR, as well as HRESI-MS, ESI-MS, UV and IR, and compared with the data reported in the literature. The acaricidal and nematocidal activities of the isolated compound 1 and its previously reported analogs 2, 3, 4 and 5 were evaluated. The results demonstrate that compounds 1, 2, 3, 4 and 5, especially compound 1, have potential as antiparasitics with acaricidal and nematocidal activities. These lactones shed new insights into the structural diversity of nemadectin and milbemycin analog libraries that are potentially accessible by combinatorial biosynthesis.

Sural S (2023) Trends Genet "Protecting axons in grandchildren."

Sural S

[Trends Genet, 2023]

Prenatal exposure to environmental agents can influence the fitness of not only the fetus, but also subsequent generations. In a recent study, Wang et al. demonstrated that feeding ursolic acid (UA), a plant-derived compound, to Caenorhabditis elegans mothers during their reproductive period prevented neurodegeneration in not only their offspring, but also the F2 progeny.

Spalthoff C et al. (2016) Neuron "Sensing pH with TMCs."

Gopfert MC, Spalthoff C

[Neuron, 2016]

Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C.elegans. In this issue of Neuron, Wang etal. (2016) report that C.elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive.

Zhang J et al. (2015) Microb Cell Fact "Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase."

Zhang J, Yan YJ, Huang SX, An J, Xiang WS, Wang XJ

[Microb Cell Fact, 2015]

BACKGROUND: Avermectin and milbemycin are important 16-membered macrolides that have been widely used as pesticides in agriculture. However, the wide use of these pesticides inevitably causes serious drug resistance, it is therefore imperative to develop new avermectin and milbemycin analogs. The biosynthetic gene clusters of avermectin and milbemycin have been identified and the biosynthetic pathways have been elucidated. Combinatorial biosynthesis by domain swap provides an efficient strategy to generate chemical diversity according to the module polyketide synthase (PKS) assembly line. RESULTS: The substitution of aveDH2-KR2 located in avermectin biosynthetic gene cluster in the industrial avermectin-producing strain Streptomyces avermitilis NA-108 with the DNA regions milDH2-ER2-KR2 located in milbemycin biosynthetic gene cluster in Streptomyces bingchenggensis led to S. avermitilis AVE-T27, which produced ivermectin B1a with high yield of 3450+/-65g/ml. The subsequent replacement of aveLAT-ACP encoding the loading module of avermectin PKS with milLAT-ACP encoding the loading module of milbemycin PKS led to strain S. avermitilis AVE-H39, which produced two new avermectin derivatives 25-ethyl and 25-methyl ivermectin (1 and 2) with yields of 951+/-46 and 2093+/-61g/ml, respectively. Compared to commercial insecticide ivermectin, the mixture of 25-methyl and 25-ethyl ivermectin (2:1=3:7) exhibited 4.6-fold increase in insecticidal activity against Caenorhabditis elegans. Moreover, the insecticidal activity of the mixture of 25-methyl and 25-ethyl ivermectin was 2.5-fold and 5.7-fold higher than that of milbemycin A3/A4 against C. elegans and the second-instar larva of Mythimna separate, respectively. CONCLUSIONS: Two new avermectin derivatives 25-methyl and 25-ethyl ivermectin were generated by the domain swap of avermectin PKS. The enhanced insecticidal activity of 25-methyl and 25-ethyl ivermectin implied the potential use as insecticide in agriculture. Furthermore, the high yield and genetic stability of the engineered strains S. avermitilis AVE-T27 and AVE-H39 suggested the enormous potential in industrial production of the commercial insecticide ivermectin and 25-methyl/25-ethyl ivermectins, respectively.